5-Day Versus 10-Day Course of Fluoroquinolones in Outpatient Males With a Urinary Tract Infection (UTI)

Geoffrey A. Mospan, PharmD, BCPS; Kurt A. Wargo, PharmD, FCCP, BCPS (AQ-ID)


J Am Board Fam Med. 2016;29(6):654-662. 

In This Article


The results of this subgroup analysis suggest that male patients with UTIs, with or without additional risk factors for cUTIs, achieved clinical success with a 5-day course of levofloxacin, rather than a traditional, prolonged course (7–14 days) of therapy. Furthermore, male patients in this analysis had clinical success similar to that of their female counterparts in both the 5-day course of levofloxacin and the 10-day course of ciprofloxacin. In addition, the results suggest that male patients with complicating risk factors have a higher rate of clinical success with a 5-day course of levofloxacin than a 10-day course of ciprofloxacin. While it would be unwise to conclude that high-dose, short-course levofloxacin should be used in all male patients with cUTIs, the data presented here support its utility for outpatient therapy.

Even though the results of this analysis are positive and suggest shorter courses of antibiotics can be considered in males with UTIs, there are limitations to this study. One caution when applying these results to the male population is to not deviate from the original inclusion and exclusion criteria, as well as the added exclusion criteria for our analysis—acute pyelonephritis. While the original study did not exclude patients with acute pyelonephritis, there were only 18 males with the diagnosis. As such, to represent a fair comparison of patients, the data from all patients with acute pyelonephritis were excluded from this analysis. Because of this, it would be inappropriate to apply these results to males with acute pyelonephritis. In addition, male patients with prostatitis, epididymitis, or perirenal abscesses were excluded from the study and should be treated according to currently recommended treatment algorithms rather than 5 days of levofloxacin. Furthermore, nearly all patients included in the study were outpatients, rather than hospitalized. Therefore it would be difficult to apply these results to hospitalized patients.

The results of this study should be applied only to susceptible microorganisms, in regions where resistance of uropathogens to levofloxacin is relatively low, and in patients with few to no risk factors for E coli resistance.[7] As stated previously, the subjects in this study were nearly entirely treated in an outpatient setting where the resistance of E coli to the fluoroquinolones was low. Therefore, attempting to infer clinical success of levofloxacin in a environment where E coli resistance to fluoroquinolones is known to be high might be futile. Several studies have demonstrated increasing resistance of uropathogens to not only levofloxacin but also other agents typically used to treat these infections.[7–9] Globally, E coli resistance to fluoroquinolones is becoming significant, ranging from 2% to 69% for those with uncomplicated, community-acquired UTIs and up to 98% for those cUTIs.[11] Because of this, it becomes important to treat such infections with the agent that has the greatest likelihood of clinical success. While a fluoroquinolone may not be the first option to treat some UTIs, it would be reasonable to treat outpatient males without previous exposure to fluoroquinolones (within the previous 4 weeks) with a 5-day course of levofloxacin 750 mg PO daily. Close follow-up to ensure resolution of symptoms is also advised, especially when the causative organism is unknown.

While the results were not reported in the previous trial, because of the small samples, in our study there were some interesting findings among those patients who clinically failed therapy. In males who received ciprofloxacin, 12 of the 14 clinical failures (85.7%) occurred with E coli as the pathogen in the ME group PT. By contrast, only 6 of the 17 clinical failures (35%) in the levofloxacin group were infected with E coli. As a result, clinical success rates for male patients initially infected with E coli were 86% and 77% for levofloxacin and ciprofloxacin, respectively.

One analysis not performed in our post hoc study was the evaluation of microbiologic eradication rates (elimination or reduction to <104 colony-forming units/mL of uropathogens at study entry), despite being performed in the original trial. In the male population, urine cultures were not available at EOT for approximately 12% of subjects in the ME group, and therefore evaluation of microbiologic eradication rates was not included as an objective of this study. For male patients in the ME group PT, however, microbiologic eradication rates were found to be 72 of 91 (79.1%) and 84 of 98 (85.7%) in the levofloxacin and ciprofloxacin groups, respectively.

Finally, the US Food and Drug Administration (FDA) recently advised health care professionals and consumers not to use fluoroquinolone antibiotics for uncomplicated infections because of increased risks of serious adverse events that outweigh the benefits of therapy.[12] Furthermore, the FDA stated that fluoroquinolones should only be used when alternative agents are not available to treat these types of infections. In the original study, the authors reported 192 patients in the levofloxacin group and 185 patients in the ciprofloxacin group had at least one adverse event; the most common were nausea, headache, and diarrhea.[10] The authors went on to state that 17 patients in the levofloxacin group and 15 in the ciprofloxacin group had significant adverse drug events. Unfortunately, they failed to report any episodes of C difficile infection, QTc prolongation, or tendon rupture—all of which can occur with these agents. Furthermore, while adverse events associated with fluoroquinolone use can occur after a single dose, the risks increase with prolonged courses.[13] Given this information and the recent advice from the FDA, it is particularly important to give the shortest, most effective duration of fluoroquinolone therapy for the treatment of complicated infections. The results of our analysis suggest that if a fluoroquinolone is used in males with a UTI, short courses may be as effective as longer courses, thereby decreasing their risk of serious adverse events.

While the results of this analysis demonstrated the utility of levofloxacin in males with cUTIs in an environment where resistance was low, an even greater finding was that the clinical success rate of a short course of antibiotics to treat cUTI was similar in male and female patients. Without question, 1 contributing factor leading to increased bacterial resistance is prolonged use of antimicrobial agents; therefore, shorter courses in males with cUTIs could help alleviate some of the resistance problems.[14,15] A larger-scale study comparing short courses of antimicrobials in males and females should be conducted to validate the results of this study. Until then, in outpatient males with cUTIs without acute pyelonephritis or other exclusions defined in this study, we recommend a duration of therapy similar to that used for female patients. Furthermore, if this strategy is used, we recommend follow-up with an appropriate health care practitioner to ensure clinical success.